Induction of neonatal sodium channel II and III alpha-isoform mRNAs in neurons and microglia after status epilepticus in the rat hippocampus

Sodium channels (NaChs) regulate neuronal excitability in both physiologica l and pathological conditions, including epilepsy and are therefore an impo rtant target for antiepileptic drugs. In the present study, we examined the distribution of mRNAs encoding neonatal NaChs II and III alpha -isoforms i n control rat hippocampus and after electrically-induced status epilepticus (SE), using nonradioactive in situ hybridization (ISH). Only weak expressi on of neonatal NaCh II and III mRNAs was observed in control hippocampus. B y contrast, increased expression of neonatal NaCh II and III mRNAs was obse rved 4 h after the induction of SE in neurons of CA1-CA3 and the dentate gr anule cell layer. These changes were detected only in rats in which SE was successfully induced and persisted, although less intense, for up to 3 mont hs, when rats display spontaneous seizures. Strong expression of neonatal N aCh alpha -isoforms was observed 1 week after SE in microglial cells, as co nfirmed by double labelling, combining ISH with immunocytochemistry for mic roglia markers. The increased expression of neonatal isoforms of the NaCh i n both neurons and microglial cells may represent a critical mechanism for modulation of neuronal excitability, glial function and pharmacological res ponse to antiepileptic drugs in the course of epileptogenesis.